N-phenyl-2-pyridinecarbothioamides as gastric mucosal protectants.
A series of substituted 2-pyridinecarbothioamides was synthesized and evaluated for gastric mucosal protectant activity in the rat. Out of this investigation N-(3,5-difluorophenyl)-2- pyridinecarbothioamide (23, AY-31,574) was identified. This compound was much more potent than sucralfate and ranitidine against ethanol-induced lesions. Compound 23 was equipotent with ranitidine against gastric injury caused by stress. Unlike ranitidine, 23 was found to be devoid of antisecretory activity in the pylorus-ligated rat model, making it a selective mucosal protectant. Such a potent selective mucosal protectant may provide a novel clinical approach in treating ulcers.
Kinney
W A
WA
Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
Lee
N E
NE
Blank
R M
RM
Demerson
C A
CA
Sarnella
C S
CS
Scherer
N T
NT
Mir
G N
GN
Borella
L E
LE
DiJoseph
J F
JF
Wells
C
C
D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D055598:Chemical Phenomena; D002621:Chemistry; D000431:Ethanol / Q000009:adverse effects; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use; D051381:Rats; D013312:Stress, Physiological / Q000150:complications; D013329:Structure-Activity Relationship; D013392:Sucralfate / Q000627:therapeutic use; D013854:Thioamides / Q000138:chemical synthesis / Q000627:therapeutic use*; D014456:Ulcer / Q000209:etiology / Q000517:prevention & control*
D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005464:Fluorobenzenes; D011725:Pyridines; D013854:Thioamides; C062456:N-(3,5-difluorophenyl)-2-pyridinecarbothioamide; D000431:Ethanol; D013392:Sucralfate; D011899:Ranitidine